Merocyanine 540-sensitized photoinactivation of leukemia cells: role of oxygen and effects on plasma membrane integrity and mitochondrial respiration.
Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. In this paper we present evidence that the MC 540-sensitized photoinactivation of leukemia cells is an oxygen-dependent process and that unsaturated plasma membrane lipids are substrates for singlet oxygen and/or other activated oxygen species generated by photoirradiated MC 540. A comparison of the inhibition of clonal growth, the inhibition of mitochondrial respiration, and the exclusion of trypan blue by the plasma membrane after exposure to MC 540 and graded doses of light showed that mitochondrial respiration is compromised relatively early in the course of the dye-mediated photoinactivation of cells, well before the plasma membrane loses its capacity to exclude trypan blue. It also showed that trypan blue exclusion assays can greatly underestimate the cytotoxic effects of MC 540-sensitized photoirradiation.
Gaffney
D K
DK
Department of Biochemistry, Medical College of Wisconsin, Milwaukee.
Schober
S L
SL
Sieber
F
F
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011744:Pyrimidinones / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005231:Fatty Acids, Unsaturated; D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; C003954:merocyanine dye; C013641:parinaric acid; D010100:Oxygen